Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure The GALACTIC Randomized Clinical Trial
Por:
Kozhuharov, N, Goudev, A, Flores, D, Maeder, MT, Walter, J, Shrestha, S, Gualandro, DM, de Oliveira, MT, Sabti, Z, Muller, B, Noveanu, M, Socrates, T, Ziller, R, Bayes-Genis, A, Sionis, A, Simon, P, Michou, E, Gujer, S, Gori, T, Wenzel, P, Pfister, O, Conen, D, Kapos, I, Kobza, R, Rickli, H, Breidthardt, T, Munzel, T, Erne, P, Mueller, C, Dimov, B, Herr, N, Isenrich, R, Mosimann, T, Twerenbold, R, Boeddinghaus, J, Nestelberger, T, Puelacher, C, Freese, M, Vogele, J, Meissner, K, Martin, J, Strebel, I, Wussler, D, Schumacher, C, Osswald, S, Vogt, F, Hilti, J, Schwarz, J, Fitze, B, Hartwiger, S, Arenja, N, Glatz, B, Rentsch, K, Bossa, A, Jallad, S, Soeiro, A, Jansen, T, Gebel, G, Bossard, M, Christ, M
Publicada:
17 dic 2019
Resumen:
IMPORTANCE Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).
OBJECTIVE To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF.
DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100mmHg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019.
INTERVENTIONS Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan.
MAIN OUTCOMES AND MEASURES The primary end pointwas a composite of all-cause mortality or rehospitalization for AHF at 180 days.
RESULTS Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P =.59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%).
CONCLUSIONS AND RELEVANCE Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.
Filiaciones:
Kozhuharov, N:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Goudev, A:
Med Univ Sofia, Queen Ioanna Univ Hosp Sofia, Dept Cardiol, Sofia, Bulgaria
Univ Hosp Queen Ioanna, Sofia, Bulgaria
Flores, D:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Maeder, MT:
Kantonsspital St Gallen, Dept Cardiol, St Gallen, Switzerland
Cantonal Hosp St Gallen, St Gallen, Switzerland
Walter, J:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Univ Basel, Univ Basel Hosp, Dept Internal Med, Basel, Switzerland
Shrestha, S:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Univ Basel, Univ Basel Hosp, Dept Internal Med, Basel, Switzerland
Gualandro, DM:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Univ Sao Paulo, Med Sch, Heart Inst INCOR, Sao Paulo, SP, Brazil
de Oliveira, MT:
Univ Sao Paulo, Med Sch, Heart Inst INCOR, Sao Paulo, SP, Brazil
Sabti, Z:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Muller, B:
Cantonal Hosp Aarau, Aarau, Switzerland
Noveanu, M:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Socrates, T:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Univ Basel, Univ Basel Hosp, Med Outpatient Dept, Basel, Switzerland
Ziller, R:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Bayes-Genis, A:
Autonomous Univ Barcelona, Dept Med, CIBERCV, Heart Inst,Hosp Univ Germans Trias & Pujol, Barcelona, Spain
Hosp Badalona Germans Trias & Pujol, Barcelona, Spain
Sionis, A:
Autonomous Univ Barcelona, Biomed Res Inst IIB St Pau, Hosp Santa Creu & St Pau, Intens Cardiac Care Unit,Cardiol Dept, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Simon, P:
Univ Hosp Basel, Clin Trial Unit, Basel, Switzerland
Michou, E:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Gujer, S:
Luzerner Kantonsspital, Dept Cardiol, Luzern, Switzerland
Kantonsspital Obwalden, Dept Internal Med, Sarnen, Eswatini
Gori, T:
Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany
Wenzel, P:
Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany
Pfister, O:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Conen, D:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Kapos, I:
Luzerner Kantonsspital, Dept Cardiol, Luzern, Switzerland
Univ Hosp Zurich, Dept Cardiol, Zurich, Switzerland
Kobza, R:
Luzerner Kantonsspital, Dept Cardiol, Luzern, Switzerland
Rickli, H:
Kantonsspital St Gallen, Dept Cardiol, St Gallen, Switzerland
Cantonal Hosp St Gallen, St Gallen, Switzerland
Breidthardt, T:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
GREAT Res Network, Rome, Italy
Univ Basel, Univ Basel Hosp, Dept Internal Med, Basel, Switzerland
Munzel, T:
Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany
Erne, P:
Luzerner Kantonsspital, Dept Cardiol, Luzern, Switzerland
Lucerne Cantonal Hosp, Luzern, Switzerland
Mueller, C:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Basel, Univ Hosp Basel, CRIB, Basel, Switzerland
Univ Hosp Basel, Basel, Switzerland
Dimov, B:
Fifth Multifunct Hosp Act Treatment, Sofia, Bulgaria
Herr, N:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Isenrich, R:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Mosimann, T:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Twerenbold, R:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Boeddinghaus, J:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Nestelberger, T:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Puelacher, C:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Freese, M:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Vogele, J:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Meissner, K:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Martin, J:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Strebel, I:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Wussler, D:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Schumacher, C:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Osswald, S:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Vogt, F:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Hilti, J:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Schwarz, J:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Fitze, B:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Hartwiger, S:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Arenja, N:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Kantonsspital Olten, Dept Cardiol, Olten, Switzerland
Glatz, B:
Univ Basel, Univ Hosp Basel, Dept Cardiol, Basel, Switzerland
Univ Hosp Basel, CRIB, Basel, Switzerland
Rentsch, K:
Univ Basel, Univ Hosp Basel, Dept Lab Med, Basel, Switzerland
Bossa, A:
Univ Sao Paulo, Med Sch, Heart Inst INCOR, Sao Paulo, SP, Brazil
Jallad, S:
Univ Sao Paulo, Med Sch, Heart Inst INCOR, Sao Paulo, SP, Brazil
Soeiro, A:
Univ Sao Paulo, Med Sch, Heart Inst INCOR, Sao Paulo, SP, Brazil
Jansen, T:
Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany
Gebel, G:
Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany
Bossard, M:
Luzerner Kantonsspital, Dept Cardiol, Luzern, Switzerland
Univ Basel, Kantonsspital Aarau, Med Univ Clin, Dept Gen Internal & Emergency Med, Aarau, Switzerland.
Univ Basel, Basel, Switzerland.
Inst Med Res, Sofia, Bulgaria.
Green Published, Green Accepted, Bronze
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